Down-regulation of TGF-β1 production restores immunogenicity in prostate cancer cells

The objective of this study is to determine if a non-immunogenic Dunning's rat prostate cancer cell line, MATLyLu, can become immunogenic by reducing the endogenous production of TGF-beta 1. An expression construct containing a DNA sequence in an antisense orientation to TGF-beta 1 (TGF-beta 1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-beta 1 reduced from 70 to 10 pg per 2 x 10(4) cells and the rate of in vitro 3H-thymidine incorporation increased 3-5 fold. After subcutaneous injection of tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the control construct, but only 43% (9/21, P <= 0.05) for cells transfected with TGF-beta 1 antisense. However, when cells were injected into immunodeficient hosts (athymic nude rats), the incidence of tumour development was 100% (10/10) for both the wild type MATLyLu cells and cells transfected with the control construct and 90% (9/10) for cells transfected with TGF-beta 1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-beta 1 is down-regulated. (C) 2000 Cancer Research Campaign